Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans

Abstract Misfolded protein oligomers are increasingly recognized as highly cytotoxic agents in a wide range of human disorders associated with protein aggregation. In this study, we assessed the possible uptake and resulting toxic effects of model protein oligomers administered to C. elegans through...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michele Perni, Benedetta Mannini, Catherine K. Xu, Janet R. Kumita, Christopher M. Dobson, Fabrizio Chiti, Michele Vendruscolo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5a3433026d44b8ebabead4cd9d9b713
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a5a3433026d44b8ebabead4cd9d9b713
record_format	dspace
spelling	oai:doaj.org-article:a5a3433026d44b8ebabead4cd9d9b7132021-12-02T16:14:09ZExogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans10.1038/s41598-021-93527-82045-2322https://doaj.org/article/a5a3433026d44b8ebabead4cd9d9b7132021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93527-8https://doaj.org/toc/2045-2322Abstract Misfolded protein oligomers are increasingly recognized as highly cytotoxic agents in a wide range of human disorders associated with protein aggregation. In this study, we assessed the possible uptake and resulting toxic effects of model protein oligomers administered to C. elegans through the culture medium. We used an automated machine-vision, high-throughput screening procedure to monitor the phenotypic changes in the worms, in combination with confocal microscopy to monitor the diffusion of the oligomers, and oxidative stress assays to detect their toxic effects. Our results suggest that the oligomers can diffuse from the intestinal lumen to other tissues, resulting in a disease phenotype. We also observed that pre-incubation of the oligomers with a molecular chaperone (αB-crystallin) or a small molecule inhibitor of protein aggregation (squalamine), reduced the oligomer absorption. These results indicate that exogenous misfolded protein oligomers can be taken up by the worms from their environment and spread across tissues, giving rise to pathological effects in regions distant from their place of absorbance.Michele PerniBenedetta ManniniCatherine K. XuJanet R. KumitaChristopher M. DobsonFabrizio ChitiMichele VendruscoloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michele Perni Benedetta Mannini Catherine K. Xu Janet R. Kumita Christopher M. Dobson Fabrizio Chiti Michele Vendruscolo Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
description	Abstract Misfolded protein oligomers are increasingly recognized as highly cytotoxic agents in a wide range of human disorders associated with protein aggregation. In this study, we assessed the possible uptake and resulting toxic effects of model protein oligomers administered to C. elegans through the culture medium. We used an automated machine-vision, high-throughput screening procedure to monitor the phenotypic changes in the worms, in combination with confocal microscopy to monitor the diffusion of the oligomers, and oxidative stress assays to detect their toxic effects. Our results suggest that the oligomers can diffuse from the intestinal lumen to other tissues, resulting in a disease phenotype. We also observed that pre-incubation of the oligomers with a molecular chaperone (αB-crystallin) or a small molecule inhibitor of protein aggregation (squalamine), reduced the oligomer absorption. These results indicate that exogenous misfolded protein oligomers can be taken up by the worms from their environment and spread across tissues, giving rise to pathological effects in regions distant from their place of absorbance.
format	article
author	Michele Perni Benedetta Mannini Catherine K. Xu Janet R. Kumita Christopher M. Dobson Fabrizio Chiti Michele Vendruscolo
author_facet	Michele Perni Benedetta Mannini Catherine K. Xu Janet R. Kumita Christopher M. Dobson Fabrizio Chiti Michele Vendruscolo
author_sort	Michele Perni
title	Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
title_short	Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
title_full	Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
title_fullStr	Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
title_full_unstemmed	Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans
title_sort	exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in c. elegans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a5a3433026d44b8ebabead4cd9d9b713
work_keys_str_mv	AT micheleperni exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT benedettamannini exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT catherinekxu exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT janetrkumita exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT christophermdobson exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT fabriziochiti exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans AT michelevendruscolo exogenousmisfoldedproteinoligomerscancrosstheintestinalbarrierandcauseadiseasephenotypeincelegans
_version_	1718384367273771008

Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans

Ejemplares similares